The key to this game is stopping the run and winning turnover battles. Aside from Mac, the biggest injury concerns are Godcheaux and Guy, both important pieces of the run defense. If those guys are out or limited, Barmore, Roberts, and others are going to have to step up against the run next to a heavily rotated Carl Davis. Bentley will be big. I don't expect to see nearly as much Mack Wilson against these bigger backs. McMillan and Jennings instead of Wilson/Uche. And yes, it may be a Tavai game.
Jon Jones largely on the speedy and dangerous Doubs. Cobbs and Lazard are solid, but don't require anything special in terms of coverage. I strongly suspect Belichick will roll out a lot of 2 high safety defenses, with the non-McCourty safety (which is a MASH unit) crashing on a run read, or perhaps starting the 2 deep coverage from a position in the box, assigned to gain depth quickly. Have to close down the middle running.
On offense, it's no mistakes. The interior OL needs to handle Clark, which should be an interesting test for Andrews and Strange, as the pure power guys have been a struggle for Andrews and are supposed to be where Strange struggles as well. Devonte Wyatt isn't even listed as a starter, but I'm going to list him as a concern as well. His snaps are limited, but he's definitely flashed, especially last week, and his combination of speed, quickness, power, and size could definitely give our OL trouble.
I don't know Jaire Alexander's status, but that will be critical.
I suspect the running game and defense will do enough so that Hoyer can steer the ship into a position where the game is not out of reach late. And call me crazy, but what the hell...I see a CB named Jones (Jack, if pressed to pick one) winning this on a late pick-6 on non-disguised coverage: Rodgers underestimates the jump the CB can get on the ball and tries to gun an out to Cobbs in at the first down marker.
This is the sort of game they have "no shot at winning" that the Patriots tend to surprise and rise to the challenge. They rally around Hoyer, lean on the defense and the run, and pull it out, just because this season the NFL is obviously like that.