Thank you for the hint, we did pin whitenoise version to 5.3.0, and it indeed solved our random connection errors.
So, there appears to be a relation; however, it is tricky (in our case) to pin down to a certain version/commit/functionality.
I also posted this as an issue in whitenoise repo:
(the only thing - I am struggling to reproduce it outside our production instance)
Just wanted to share that I had this error show up for me today for the first time. I am using whitenoise==6.6.0 It is a bit strange though as I have had this project running for many months now and never experienced any problems before. even now it seems to be only 2 or 3 requests in a thousand