Can't understand why a Lisp would be hard to build on a Mac or elsewhere. What are the dependencies besides some common C libraries (e.g. for math, unicode handling, etc)?
Huge number of complex and extremely platform-specific dependencies and modules, like garbage collectors, foreign function interfaces, native code generators, etc, etc. All inherently very platform-specific, fragile, and dependent on specific tooling. Very much not plain C code.
It is not unique to guile either. Compiling things on Mac os brings back memories from Redhat 8. I have had so much more luck with WSL or even cygwin than Mac os for at least a dozen open source apps.