Information theory to a large extent deals with how to efficiently encode messages given a probability distribution over messages.
Intuitively, it seems like we can think of machine instructions (or programs) as "messages to the CPU". Some messages are more probable than others. E.g. "add numbers x and y" is more probable than "compute the y'th square root of x", which is maybe one of the reasons why we don't have an instruction like the latter.
However there are obviously other considerations involved like computational complexity, so it doesnt seem obvious to me how information theory can be used to understand instruction set architectures. Has information theory been apllied to understand insteuction set archtectures? (I didnt find anything after a quick google search.)