The I2C pins that I was referencing have FT as their pin I/O structure. According to the app note, that corresponds to a five-volt tolerant pin. Though the pin structures have some underscore characters, they do have FT in their name (FT_fa and FT_fha); i can't find info on those subscripts . All of that is leading me to believe that it should be safe to run with a pull up resistor to 5 volts.
To be sure, I'm referencing the datasheet of the processor with the portenta schematic, making sure to match the correct processor pins with the I2C port im using in my app, in this case I2C3. That's the one going to the GPIO pins on the portenta and the jst connector.