Windows printer drivers can take over the port and will typically poll the port either occasionally or constantly (Epson is particularly bad) to determine if the printer is still attached, needs ink, etc. If your print spooler has anything in it waiting to print, (or sometimes even if it doesn't) it will also poke its head in to see what's going on with the port.
These activities can interfere with Mach's port driver. Many people have posted here that removing a printer driver cleared up a random port problem, and it stands to reason considergin how the PC communicates internally.