I'm having similar issues. Every few days, sometimes after about a week, my unraid server will go very unresponsive. One thing I've noticed is that my memory utilization is going way up. I have Plex transcoding to memory and it doesn't seem to be cleaning up the transcode files after upgrading to 6.12.x. I'll have large files in there eating up almost all of the 32GB ram I have. I think the server is just choking on running out of memory. Frustratingly, this worked perfectly fine prior to 6.12.x (my unraid box has been chugging along for about six years now...).
I'm wondering if others with the unresponsive server issue are also running plex and transcoding to memory. I grabbed an old nvme drive to transcode to instead, made the change this morning, and will see if that stablizes things for me.