I just switched from Windows 8.1 to Windows 10 a few months ago.
I installed Windows Enterprise 10.0.19045.2604 and Pegasus Mail 4.73.639, Mar 30 2018, build 639, later I switched to Pegasus Mail 4.80.1028, Jan 16 2022, build 1028.
The problem is always the same: I can receive and send emails, but not emails with a larger attachment (approx. > 10 MB). If I try this, Pegasus Mail starts sending and at some point at 27% or 75% (depending on the size of the mail, numbers are only examples) it breaks off. Much worser: The entire Internet connection (RJ45-LAN via cable modem) breaks down. To get access to the Internet again, I have to unplug the rj45 connector and plug it back in.
At first I suspected my email provider, but an email address from a completely different provider shows the same behavior.
I also tried all kind of secure connections, STARTTLS, SSL etc., without success.

What the heck is this? In the meantime I've switched to Thunderbird, which actually is a piece of crap.....

One thing for certain is that Pegasua Mail won't affect your LAN connection. The only thing that I think might be contribute to the problem from the Pegasus Mail side is that the internet connection timeout is too short allowing the connection to timeout before the send finishes. I suggest setting SMTP the timeout to 120 and see if that makes a difference.

Beyond that, I don't know why Thunderbird would work and Pegasus Mail won't. I assume you have duplicated the working SMTP settings in TB to Pegasus Mail.

Have you tried tools / internet options / create internt session logs.
Then try the connection, and afterwards examine the smtp log in TCPLogs subdirectory.
Perhaps it may show some kind of message??

I had exactly the same problem when I migrated from Windows 10 to Windows 11 (a disaster on itself). Running Winpm-32.exe in compatibility mode with Windows 8 solved the problem, at least in my case. Transmission seems to be somewhat slower though. Thus: go to the folder where your Pegasus program files are located (in my case
C:\Program Files (x86)\Pegasus\Programs) and right click on winpm-32.exe. Click 'properties' and then click the 'compatibilty' tab. Then check 'Run in compatibility mode for' and then in the drop down menu choose Windows 8 or 7. Click apply and then OK.
Hope it helps

This Pegasus Mail installation should only be functioning if the mailbox directory(ies) are located somewhere else. In Window 10 and 11, the Program Files directories are protected which prevent the routine updating of configuration files done by Pegasus Mail. It is strongly recommended that Pegasus Mail be installed in the default location of C:\ or a manually created subdirectory of C: (eg: C:\Apps). No compatibility mode is needed.