Exchange Back pressure is real. I have setup two separate domains in my lab (northwindtrader.com and constoso.com). On northwindtrader.com domain I am testing migrating Exchange 2013 CU21 to Exchange 2019. I have not introduced Exchange 2019 yet in the domain yet. I want to make sure mail flow is smooth between the two domain before I do the migration. Suddenly, outgoing mails on northwindtrader.com exchange started queuing up and no mails were delivered to exchange server in contoso.com. Incoming mail was fine. Initially, I put all my efforts trying to troubleshoot on northwindtrader.com exchange server. Properties of mail queued showed the following.

Error message:
452 4.3.1 Insufficient System resources

Make sure to turn on the protocol logging on exchange server for further troubleshooting. A send log file under c:\Program Files\Microsoft\Exchange Server\V15\TransportRoles\Logs\Hub\ProtocolLog\SmtpSend gave enough clue.

o the 4.3.1 Insufficient system resources message was coming from the IP associated to Exchange server on consoto.com . Surely enough, Contoso.com Exchange server was running low on C: drive space. I added more space and rebooted. No outgoing or email issue any more.