No idea. Since the path is a /run/media one, what’s the filesystem used there? Perhaps it’s incompatible. Have you tried putting the iso in your home directory and going from there instead?

But perhaps it would work best if you just do what the documentation tells you not to do and rpm-ostree install virt-manager (and libvirt and friends, if needed)

That /run/user/1000/doc/… path suggests it’s getting the .iso through the documents portal. So virt-manager is a flatpak? Sounds bad! Try using flatseal to give it direct access to all files.

Check the generic HD audio instead of USB audio. Or are those empty?

In alsamixer, is line unmuted and at a reasonable volume level and is “loopback mixing” enabled? Make sure you check on your actual soundcard, not the PipeWire fake card. And in any PulseAudio control panel (pavucontrol for example) make sure it’s set to the right port.