I wonder if this is relevant/helpful: https://itsfoss.com/systemd-sysext/

Newer instructions by the same author: http://sam-d.com/blog//running-guix-package-manager-on-top-of-fedora-silverblue-updated-instructions/

@paequ2 Well, this appears to be somewhat out of date now. I would say that I have managed to bork systems in the past, but it hasn’t happened in the last 15 months, so I think bugs have been shaken out of the system and it is very stable today (just do not under any circumstances touch the store!)

Good luck running it on Silverblue, please let us know how you get on.