It will reply to anyone inside your environment by default. If you enable Out of Office replies to the Internet, it will reply to external emails as well.
Keep in mind that enabling OOF to the Internet is generally not recommended for several reasons, not the least of which is an increase in spam.
Exchange has no way of knowing whether remote servers are going to be Exchange or not. Additionally, it has no way of knowing if the receiving user is using Outlook or not.
It's enabled internally, and can be enabled/disabled externally.
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