No way ND should lose this game. "Win one for Sark" is great and all but football is still a lot about the X's & O's. Losing you HC in the middle of the season is going to have a huge impact on how they prepare for this game.
I disagree that losing HC will have that much impact on those parts of the game. Much of the Xs and Ox come from the coordinators and the coaching is predominantly from position coaches. One of most crucial set of decisions made by the HC is the hiring of assistants.
What likely will change is more philosophical, such as aggressiveness in the play calling.