Looking at the results of the last match when Lyon lost to Strasbourg then Manchester United should be able to beat Lyon but it is not certain that this can be done by Manchester United. I still see the chance of a draw in this match and if one of them wins I will choose Manchester United. Lyon did not show a good game at all against Strasbourg and this is a big worry when they face Manchester United who are much more dangerous in attack so if they are not prepared well it will make Lyon experience bad results again.
Lyon are playing their Ligue 1 games without their manager Fonseca. I assume you know about Fonseca's nine-month ban. It is valid only there. Not in the Europa League. Therefore I wouldn't be affected by that Strasbourg loss very much honestly.
They haven't been losing in the Europa League for 7 games. That's a pretty good record.
I don't think they will surrender easily against the Red Devils. I even think Lyon can advance to the semi finals in case they get a decent win home in the first leg.