While the leagues are of course vastly different, Lyon is doing a bit better if I am not wrong. They have 45 points in 26 games, which is about 1.73 points per game, and fifth place at Ligue 1 as well. Whereas United has 37 points in 29 games, which is about 1.27 points per game, and they are 13th in the league. I am not comparing ligue 1 with premier league, of course premier league is harder to do better but that doesn't mean these two teams are close to each other normally.
Just because United is United, people see a chance for them to win, after all they got here so far, so they have a chance to move further too. But I would say if we were to compare seasons, Lyon has been better this season overall than United.
Like you mentioned, premier league and French league are vastly different. Plus, we have seen plenty of teams that did terrible at league and still won the whole thing here, it is not a shocker and it happens. So we could consider this game to be similar to that logic. Just because Lyon looks decent at their league at the moment, doesn't mean they are better, United could still win this game and odds are showing it.
Lyon and United are close in my mind, I have no clue if they are actually as close as I believe, but to me there is a very big chance that this could go to penalties. A tie in both games, or at least on aggregate sounds like a big possibility to me too. Betting on this game will be hard no matter which side we pick.