A transient failure has occurred. MSExchange System Attendant Mailbox event id 4001

hello! we have an ongoing problem, where our exchange server keeps dropping connections- and services become unavailable
the event that we get at the time this happens is the following

MSExchange System Attendant - Event ID 4001
A transient failure has occurred. The problem may resolve itself in awhile. The service will retry in 56 seconds. Diagnostic information:
Cannot open mailbox

we then receive the following event

MSExchangeMailSubmission - Event ID 1009
The Microsoft Exchange Mail Submission Service is currently unable to contact any Hub Transport servers in the local Active Directory site. The servers may be too busy to accept new connections at this time.

we then get

MSExchange ActiveSync - 1022
The connection between the Client Access server and Mailbox server "server.int" failed.

followed by

MSExchangeIS - 10025
There are 20 RPC requests that take abnormally long time to complete. It may be indicative of performance problems with your server.

any ideas? this has been happening every other couple of days and kills everyones exchange connection for a couple of minutes
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jsctechyInfrastructure Team LeadAsked:
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Jeremy WeisingerSenior Network Consultant / EngineerCommented:
Check what the server is doing at these times. It could be some other process is using all the server's resources (like a backup maybe).

It could also be hardware issues. Have you gone through the System event log?
jsctechyInfrastructure Team LeadAuthor Commented:
there is an email that goes out every morning that they are suspecting is causing this, but the email is only 38kb, going to about 300 recipients
Jeremy WeisingerSenior Network Consultant / EngineerCommented:
Do the issues occur when the email is going out?

Do you have any restrictions on the Hub Transport max connection limit?

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jsctechyInfrastructure Team LeadAuthor Commented:
Maximum Concurrent Outbound Connections - 1000
Maximum Concurrent Outbound Connections Per Domain - 5
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