The documentation says tweaks.native_hls_parsing makes the underlying player of Safari fetch and parse the HLS playlists in lieu of the Bitmovin Player.
This results in requests returning 416 network errors (416 Requested Range Not Satisfiable) as I could confirm by reproducing the issue manually.
Safari 15.5 was officially launched with the issue fix in the new WebKit engine. It’s now available in macOS Monterey 12.4, macOS Big Sur, macOS Catalina, iPadOS 15.5, and iOS 15.5.
It looks a related fix was stated in the Safari’s release note too, although I think the issue was not limited to audio.
Fixed playback of HTML5 embedded audio with unbounded range requests