Nearly all emails are getting blocked as spam.

Came in to the office this morning and noticed the quarantine report email I got was much much larger than the one that I normally get. Lots of valid emails were blocked as spam and I had to release them. These emails came from senders that I had previously sent and received mail from with no issue and we have not changed any settings recently, so I am not sure why they are getting quarantined. 

One strange thing that is happening is some emails will get through just fine, when I reply and they respond back it will quarantine their second email, even though it just let the first one through just fine. Checking in Central Admin all of the emails that get blocked are for Spam. I can't find any more specific details anywhere on why they are being classified as spam. 

This is happening for everyone in our domain. No blocks in the allow/block list.

Tangent: Anyone ever seen this error in an NDR?
554 5.7.1 Service unavailable; Sender address [ (EMAIL) ] blocked using 

A customer that we have set up email protection for blocks all mail from our domain and this is the NDR we get. Have a support case open currently, but curious if anyone has seen this before.