Key matchups to keep an eye on as the Seattle Seahawks take on the San Francisco 49ers in Week 6

With Lucas still on the PUP list, Forsythe will be tasked with dealing with Bosa, which based on past precedent doesn't bode well for the Seahawks. The fourth-year tackle started the first game between these rivals last year in Santa Clara and allowed five pressures and two sacks, struggling to protect Geno Smith while seeing extensive reps against the superstar pass rusher. Interestingly, however, after checking in as a substitute in a home game in 2021, he held up well against Bosa in limited snaps and didn't give up the pressure on six pass block reps. For Seattle to have any chance of winning on Thursday night, it will be essential to provide additional support to whoever Bosa faces to prevent him from destroying the schedule on his own.

—Seahawks linebackers Tyrel Dodson and Jerome Baker against 49ers running back Jordan Mason: Dodson and Baker were in the starting lineup together for just the third time last week against the Giants and didn't execute their run fits consistently, leading to Tyrone Tracy scoring big runs for 175 rushing yards in the disappointing upset loss. They'll need to be at their highest level of communication on Thursday night, making sure they're on the same page with the rest of the defense and understanding where to attack to ensure those gaps aren't left wide open on the 49ers roster that has been in the past has excelled at providing those opportunities to his running backs.

A typical example? Despite star Christian McCaffrey being sidelined with an Achilles tendon injury, Mason ranks second in the NFL in rushing yards, second in runs of 20 yards and fifth in rushing first downs, and is thriving in Kyle Shanahan's back-friendly scheme behind a solid offensive line . A more physical downhill player than McCaffrey, Mason leads the NFL in yards after contact (340) and forced missed tackles (25). So not only do Seattle's linebackers need to do a much better job of executing run fits, but they better be ready to finish or else San Francisco will have a big day picking up extra yards, which is what happened on Thursday night would be a recipe for disaster.

—Seahawks tight ends Noah Fant, AJ Barner and Pharoah Brown versus 49ers safeties Ji'Ayir Brown and Malik Mustapha: Statistically, the 49ers have done quite well against tight ends this season, ranking 11th in receptions allowed and fifth in receiving yards allowed at the position. However, they have given up two touchdowns to tight ends and compared to their previous five opponents, the Seahawks will pose far greater challenges in coverage with receivers DK Metcalf, Jaxon Smith-Njigba and Tyler Lockett. Without injured All-Pro Talanoa Hufanga, Brown and Mustapha each gave up a touchdown in coverage, with Mustapha allowing a score to Patriots tight end Austin Hooper in Week 4.

Given Seattle's talented receiving corps, the pressure will be off on Brown and Mustapha to handle one-on-one coverage against Fant and Barner, who have combined to catch 20 passes for 188 yards and a touchdown so far. While they haven't been a big part of Ryan Grubb's passing game yet, the two players have been more productive in recent weeks, suggesting the new game manager has started to figure out how to use them as complementary targets. In a game that relies on getting the ball out of Smith's hands quickly, the tight ends could be viable options to move the chains and potentially do some damage on Thursday night.

—The Seahawks outside linebackers Boye Mafe, Derick Hall and Dre'Mont Jones against the 49ers tackle Trent Williams and Colton McKivitz: Williams and McKivitz continue to be the strength of San Francisco's offensive line and have played well through the first five games, although they haven't necessarily been dominant in pass protection. Both tackles allowed at least 11 pressures, while McKivitz ranks second in the NFL with five quarterback hits allowed, so opponents found some success running off the edge against the 49ers. Where they could cause the Seahawks the most problems, however, is in the run game, where they have ranked in the top 11 in PFF run block ratings so far and have been particularly effective in zone schemes.

Losing Uchenna Nwosu after playing just 20 snaps in his season debut could spell doom for the Seahawks in that regard. He's their best edge defender against the run, and with both Mafe and Hall playing less than 100 percent and Jones struggling at times this year, the 49ers will look to take advantage by running out of the tackle as much as possible . If Seattle wants to counteract that, it might be worth bringing 6-5, 300-pound Mike Morris into the lineup at outside edge, a position he previously played at Michigan. His length and physicality could pay dividends by giving this particular opponent an advantage in a rotational role.

—Seahawks running backs Ken Walker III and Zach Charbonnet versus 49ers linebackers Fred Warner and DeVondre Campbell: After giving his running backs the ball just seven total times on Sunday, Grubb accepted the blame for not running the ball more often against the Giants, and he can't afford to play such a one-dimensional offensive game plan against the 49ers. Walker hasn't had much luck against San Francisco in the past, failing to rush for more than 47 yards in any of his three previous regular season games against San Francisco. However, he had success in the Wild Card round two years ago, rushing for 63 yards and a touchdown, and he also won't face defenses of the same caliber as he has in recent years.

While Warner has continued to perform at an All-Pro level this season, San Francisco's losses on defense, including the loss of Arik Armstead and the loss of Javon Hargrave to a season-ending injury, have left the team vulnerable at center. Campbell also struggled with missed tackles, replacing the injured Dre Greenlaw, who is currently second on the team with six missed tackles in five games. Because of these issues, they rank 21st in the NFL in yards per carry allowed, down nearly 10 spots from a year ago. So the Seahawks should be able to find traction on the floor if they stick with it early to withstand some pressure away from Smith and the offensive line.

—Seahawks cornerbacks Devon Witherspoon, Tre Brown and Nehemiah Pritchett versus 49ers receivers Brandon Aiyuk, Deebo Samuel and Jauan Jennings: At full strength, this might be the most compelling matchup on either side of the football, as the Seahawks have one of the best young cornerback groups in the NFL and the 49ers have a dynamic trio of wideouts catching passes from Brock Purdy. But an ankle injury will keep Riq Woolen out Thursday night, shifting the advantage in San Francisco's favor as either Pritchett makes his first NFL start in his NFL career or veteran Artie Burns moves from the practice squad to the lineup. Both options result in significant talent losses that Shanahan can look to exploit.

Athletically, Pritchett ran a 4.36 40-yard dash from Auburn, so he has the skills to keep up with a speedster the caliber of Aiyuk or Samuel. However, he only has 12 defensive snaps under his belt, and although he broke up a pass last week, he also got burned in coverage by Darius Slayton and was lucky to have Daniel Jones trip up the receiver in the end zone. As for Burns, he's started nearly 40 games in the league, but he still hasn't gotten many regular-season snaps in the slot, and facing Samuel and Aiyuk could be a major mismatch for him. Add in Jennings' size and catch radius against Brown and Witherspoon, and you may have a matchup where the 49ers now have the edge in prime time.